Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy
Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy
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DOI：
10.1038/modpathol.2014.136
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发表时间：
2015-04-01
期刊：
影响因子：
7.5
通讯作者：
Cheng, Liang
中科院分区：
文献类型：
--
作者：
Bradish, Joshua R.;Richey, Justin D.;Cheng, Liang
全身性靶向分子治疗（以选择性BRAF抑制剂的形式存在或不存在MEK抑制剂）是患有BRAF V600突变阳性黑色素瘤且患有不可切除的III期和IV期疾病的患者的标准治疗。BRAF突变阴性的原发性肿瘤患者可能表现为BRAF突变阳性的转移性疾病。目前尚不清楚是否所有转移性病变都携带与原发性肿瘤相同的BRAF突变状态，以及是否存在不一致性，其发生频率如何。使用BRAF RGQ PCR试剂盒（Qiagen）测试25名黑素瘤患者中的原发性和匹配的转移性病灶的BRAF V600 E/Ec、V600 K、V600 D和V600 R突变。4例患者（16%）的原发性和转移性黑色素瘤BRAF状态之间存在差异。在这些患者中，2例（8%）患者患有BRAF突变阳性原发性黑色素瘤伴BRAF突变阴性转移性病灶，2例（8%）患者患有BRAF突变阴性黑色素瘤伴BRAF突变阳性转移性病灶。总之，BRAF突变状态的不一致性在原发性和转移性黑色素瘤之间并不罕见。对于既往阴性患者，确定新转移性肿瘤的BRAF突变状态以正确分配BRAF抑制剂治疗可能是谨慎的。不一致的BRAF状态可能在BRAF抑制剂治疗中观察到的不同应答模式和不可避免的耐药性中发挥作用。
Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.